The Pathogenic Role of Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in the Nocardiosis with the Central Nervous System Involvement

Yu-Fang Lo, Shang-Yu Wang, Yi-Hui Wu, Mao-Wang Ho, Chun-Fu Yeh, Tsai-Yi Wu, Jhan-Jie Peng, You-Ning Lin, Jing-Ya Ding, Han-Po Shih, Chia-Chi Lo, Yu-Pei Chan, Cheng-Shyuan Rau, Chen-Yen Kuo, Kun-Hua Tu, Wei-Te Lei, Yi-Chun Chen, Cheng-Lung Ku

Research output: Contribution to journalJournal Article peer-review

Abstract

PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients.

METHODS: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients.

RESULTS: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated.

CONCLUSION: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.

Original languageEnglish
Article number176
Pages (from-to)176
JournalJournal of Clinical Immunology
Volume44
Issue number8
DOIs
StatePublished - 12 08 2024

Bibliographical note

Publisher Copyright:
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.

Keywords

  • Humans
  • Autoantibodies/immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor/immunology
  • Nocardia Infections/immunology
  • Female
  • Male
  • Middle Aged
  • Aged
  • Adult
  • Pulmonary Alveolar Proteinosis/immunology
  • Cryptococcus gattii/immunology
  • Cryptococcus gattii
  • Nocardiosis
  • Pulmonary alveolar proteinosis
  • Central nervous system infection
  • Anti-GM-CSF autoantibody

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